Multi-sensor patient monitor to detect impending cardiac decompensation

ABSTRACT

A system for detecting impending acute cardiac decompensation of a patient includes impedance circuitry, an activity sensor, and a processor system. The impedance circuitry measures a hydration signal of the patient, wherein the hydration signal corresponds to a tissue hydration of the patient. The activity sensor to measure an activity level of the patient, and the processor system includes a computer readable memory in communication with the impedance circuitry and the activity sensor, wherein the computer readable memory of the processor system embodies instructions to combine the hydration signal and the activity level of the patient to detect the impending acute cardiac decompensation.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present application claims the benefit under 35 USC 119(e) of U.S.Provisional Application Nos. 60/972,512 and 60/972,537 both filed Sep.14, 2007, and 61/055,666 filed May 23, 2008; the full disclosures ofwhich are incorporated herein by reference in their entirety.

The subject matter of the present application is related to thefollowing applications: 60/972,329; 60/972,354; 60/972,616; 60/972,363;60/972,343; 60/972,581; 60/972,629; 60/972,316; 60/972,333; 60/972,359;60/972,336; 60/972,340 all of which were filed on Sep. 14, 2007;61/046,196 filed Apr. 18, 2008; 61/047,875 filed Apr. 25, 2008;61/055,645, 61/055,656, 61/055,662 all filed May 23, 2008; and61/079,746 filed Jul. 10, 2008.

The following applications are being filed concurrently with the presentapplication, on Sep. 12, 2008: 026843-000220US entitled “Adherent Devicewith Multiple Physiological Sensors”; 026843-000410US entitled“Injectable Device for Physiological Monitoring”; 026843-000510USentitled “Delivery System for Injectable Physiological MonitoringSystem”; 026843-000620US entitled “Adherent Device for Cardiac RhythmManagement”; 026843-000710US entitled “Adherent Device for RespiratoryMonitoring”; 026843-000810US entitled “Adherent Athletic Monitor”;026843-000910US entitled “Adherent Emergency Monitor”; 026843-001320USentitled “Adherent Device with Physiological Sensors”; 026843-001410USentitled “Medical Device Automatic Start-up upon Contact to PatientTissue”; 026843-001900US entitled “System and Methods for Wireless BodyFluid Monitoring”; 026843-002010US entitled “Adherent Cardiac Monitorwith Advanced Sensing Capabilities”; 026843-002410US entitled “AdherentDevice for Sleep Disordered Breathing”; 026843-002710US entitled“Dynamic Pairing of Patients to Data Collection Gateways”;026843-003010US entitled “Adherent Multi-Sensor Device with ImplantableDevice Communications Capabilities”; 026843-003110US entitled “DataCollection in a Multi-Sensor Patient Monitor”; 026843-003210US entitled“Adherent Multi-Sensor Device with Empathic Monitoring”; 026843-003310USentitled “Energy Management for Adherent Patient Monitor”; and026843-003410US entitled “Tracking and Security for Adherent PatientMonitor.”

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to patient monitoring, and morespecifically to patient monitoring to detect and/or avoid impendingcardiac decompensation. Although embodiments make specific reference tomonitoring impedance and electrocardiogram signals with an adherentpatch, the system methods and device described herein may be applicableto many applications in which physiological monitoring is used, forexample wireless physiological monitoring with implantable devices forextended periods.

Patients are often treated for diseases and/or conditions associatedwith a compromised status of the patient, for example a compromisedphysiologic status such as heart disease. In some instances a patientmay have suffered a heart attack and require care and/or monitoringafter release from the hospital. While such long term care may be atleast partially effective, many patients are not sufficiently monitoredand eventually succumb to cardiac decompensation, or heart failure. Oneexample of a device that may be used to monitor a patient is the Holtermonitor, or ambulatory electrocardiography device. Although such adevice may be effective in measuring electrocardiography, suchmeasurements alone may not be sufficient to reliably detect and/or avoidan impending cardiac decompensation.

In addition to measuring heart signals with electrocardiograms, knownphysiologic measurements include impedance measurements. For example,transthoracic impedance measurements can be used to measure hydrationand respiration. Although transthoracic measurements can be useful, suchmeasurements may use electrodes that are positioned across the midlineof the patient, and may be somewhat uncomfortable and/or cumbersome forthe patient to wear.

Work in relation to embodiments of the present invention suggests thatknown methods and apparatus for long term monitoring of patients may beless than ideal to detect and/or avoid an impending cardiacdecompensation. In at least some instances, cardiac decompensation canbe difficult to detect, for example in the early stages. At least someof the known devices may not collect the right kinds of data to treatpatients optimally. For example, although successful at detecting andstoring electrocardiogram signals, devices such as the Holter monitorcan be somewhat bulky and may not collect all of the kinds of data thatwould be ideal to diagnose and/or treat a patient, for example to detectdecompensation. In at least some instances, devices that are worn by thepatient may be somewhat uncomfortable, which may lead to patients notwearing the devices and not complying with direction from the healthcare provider, such that data collected may be less than ideal. Althoughimplantable devices may be used in some instances, many of these devicescan be invasive and/or costly, and may suffer at least some of theshortcomings of known wearable devices. As a result, at least somepatient are not adequately monitored, and may go into cardiacdecompensation, or even die. Work in relation to embodiments of thepresent invention suggests that improved monitoring may avoid patienttrauma, save lives, and decrease health care costs.

Therefore, a need exists for improved patient monitoring. Ideally, suchimproved patient monitoring would avoid at least some of theshort-comings of the present methods and devices.

2. Description of the Background Art

The following U.S. patents and Publications may describe relevantbackground art: U.S. Pat. Nos. 4,121,573; 4,955,381; 4,981,139;5,080,099; 5,353,793; 5,469,859; 5,511,553; 5,544,661; 5,558,638;5,724,025; 5,772,586; 5,862,802; 6,047,203; 6,117,077; 6,129,744;6,225,901; 6,308,094; 6,385,473; 6,416,471; 6,454,707; 6,454,708;6,527,711; 6,527,729; 6,551,252; 6,595,927; 6,595,929; 6,605,038;6,645,153; 6,821,249; 6,980,851; 7,020,508; 7,054,679; 7,153,262;7,160,252; 2004/133079; 2004/152956; 2005/0113703; 2005/0131288;2006/0010090; 2006/0031102; 2006/0089679; 2006/122474; 2006/0155183;2006/0224051; 2006/0264730; 2007/0021678; 2007/0038038; 2005/256418;2005/137626; and 2006/161459. The following PCT Publication(s) may alsodescribe relevant background art: WO2006/111878.

BRIEF SUMMARY OF THE INVENTION

Embodiments of the present invention provide systems and methods for thedetection of an impending cardiac decompensation. In many embodiments,the impending decompensation can be detected early enough to avoid, orat least delay, the impending decompensation, such that patient traumaand/or expensive ICU care can be avoided. Although embodiments makespecific reference to monitoring impedance and electrocardiogram signalswith an adherent patch, the system methods and device described hereinmay be applicable to many applications in which physiological monitoringis used, for example wireless physiological monitoring with implantedsensors for extended periods.

In a first aspect, embodiments of the present invention provide a methodof detecting an impending cardiac decompensation of a patient. At leasttwo of an electrocardiogram signal of the patient, a hydration signal ofthe patient, a respiration signal of the patient or an activity signalof the patient are measured. The at least two of the electrocardiogramsignal, the hydration signal, the respiration signal or the activitysignal are combined to detect the impending cardiac decompensation. Inmany embodiments, the impending decompensation can be detected at least24 hours before the decompensation occurs, for example 72 hours, and inmany embodiments with a confidence level of at least 80%, for example90%.

In many embodiments, the at least two comprise at least three of theelectrocardiogram signal, the hydration signal, the respiration signalor the activity signal, and the at least three are measured and combinedto detect the impending cardiac decompensation. In specific embodiments,the at least three comprise at least four of the electrocardiogramsignal, the hydration signal, the respiration signal or the activitysignal, and the at least four are measured and combined to detect theimpending cardiac decompensation.

In specific embodiments, the electrocardiogram signal, the hydrationsignal, the respiration signal and the activity signal are measuredcombined to detect the impending cardiac decompensation.

In many embodiments, the at least two of the electrocardiogram signal,the hydration signal, the respiration signal or the activity signal canbe used simultaneously to determine impending cardiac decompensation.The at least two signals can be used simultaneously in many ways.

In many embodiments, combining comprises using the at least two of theelectrocardiogram signal, the hydration signal, the respiration signalor the activity signal to look up a value in a previously existingarray. In some embodiments, combining may comprise at least one ofadding, subtracting, multiplying, scaling or dividing the at least twoof the electrocardiogram signal, the hydration signal, the respirationsignal or the activity signal. In some embodiments, the at least two ofthe electrocardiogram signal, the hydration signal, the respirationsignal or the activity signal can be combined with at least one of aweighted combination, a tiered combination or a logic gated combination,a time weighted combination or a rate of change.

In many embodiments, a flag status is determined in response to the atleast two of the electrocardiogram signal, the hydration signal, therespiration signal or the activity signal. The flag status can bedetermined in response to a change in the at least two of theelectrocardiogram signal, the hydration signal, the respiration signalor the activity signal. In some embodiments, additional signalmeasurements of the patient can be made in response to the flag status.

In many embodiments, the at least two of the electrocardiogram signal,the hydration signal, the respiration signal or the activity signal arecombined in response to a time of day.

In many embodiments, the at least two of the electrocardiogram signal,the hydration signal, the respiration signal or the activity signal maycomprise at least one of a derived signal, a time averaged signal, afiltered signal or a raw signal.

In many embodiments, baseline values of the patient for the at least twoof the electrocardiogram signal, the hydration signal, the respirationsignal or the activity signal are determined, and the at least two ofthe electrocardiogram signal, the hydration signal, the respirationsignal or the activity signal signals comprise changes from the baselinevalues.

In many embodiments, the at least two of the electrocardiogram signal,the hydration signal, the respiration signal or the activity signalcomprise differences from population baseline values, and the impendingdecompensation is detected in response to the differences from thebaseline values of the patient population.

In many embodiments, the hydration signal comprises an impedance signaland the activity signal comprise an accelerometer signal.

In many embodiments, the activity signal may comprise an accelerometersignal to indicate a posture of the patient. In specific embodiments,the accelerometer signal may comprise a three dimensional inclinationsignal to determine a three dimensional orientation of the patient.

In many embodiments, a temperature signal is combined with the at leasttwo of the electrocardiogram signal, the hydration signal, therespiration signal or the activity signal to detect the impendingcardiac decompensation.

In many embodiments, the at least two of the electrocardiogram signal,the hydration signal, the respiration signal or the activity signal aretransmitted to a remote site where the at least two of theelectrocardiogram signal, the hydration signal, the respiration signalor the activity signal are combined to detect the impending cardiacdecompensation.

In many embodiments, instructions are transmitted from a remote site toa processor supported with the patient, and the at least two of theelectrocardiogram signal, the hydration signal, the respiration signalor the activity signal are combined with the processor in response tothe instructions to detect the impending cardiac decompensation.

In another aspect, embodiments of the present invention provide a systemto detect impending cardiac decompensation of a patient. The systemcomprises circuitry to measure at least two of an electrocardiogramsignal of the patient, a hydration signal of the patient, or an activitysignal of the patient. A processor system comprising a tangible mediumin communication with the circuitry is configured to combine the atleast two of the electrocardiogram signal, the hydration signal, therespiration signal or the activity signal to detect the impendingcardiac decompensation.

In some embodiments, the processor system comprises a least oneprocessor remote from the patient configured to combine the at least twoto detect the decompensation.

In some embodiments, the processor system comprises a processorsupported with the patient configured to receive instructionstransmitted from a remote site and combine the at least two in responseto the instructions to detect the impending cardiac decompensation.

In many embodiments, the at least two comprise at least three of theelectrocardiogram signal, the hydration signal, the respiration signalor the activity signal and the at least three are measured and combinedto detect the impending cardiac decompensation. In specific embodiments,the at least three comprise at least four of the electrocardiogramsignal, the hydration signal, the respiration signal or the activitysignal and the at least four are measured and combined to detect theimpending cardiac decompensation.

In specific embodiments, the processor system simultaneously uses the atleast two of the electrocardiogram signal, the hydration signal, therespiration signal or the activity signal to determine impending cardiacdecompensation. The at least two signals can be used simultaneously inmany ways,

In many embodiments, combining comprises the processor system using theat least two of the electrocardiogram signal, the hydration signal, therespiration signal or the activity signal to look up a value in apreviously existing array. In some embodiments, combining comprises atleast one of adding, subtracting, multiplying, scaling or dividing theat least two of the electrocardiogram signal, the hydration signal, therespiration signal or the activity signal. In some embodiments, the atleast two of the electrocardiogram signal, the hydration signal, therespiration signal, or the activity signal can be combined with at leastone of a weighted combination, a tiered combination or a logic gatedcombination, a time weighted combination or a rate of change.

In many embodiments, the processor system determines a flag status inresponse to the at least two of the electrocardiogram signal, thehydration signal, the respiration signal or the activity signal. Theprocessor system determines the flag status in response to a change inthe at least two of the electrocardiogram signal, the hydration signal,the respiration signal or the activity signal. In some embodiments, theprocessor system affects the circuitry to make additional signalmeasurements of the patient in response to the flag status.

In many embodiments, the processor system combines the at least two ofthe electrocardiogram signal, the hydration signal, the respirationsignal or the activity signal in response to a time of day.

In many embodiments, the at least two of the electrocardiogram signal,the hydration signal, the respiration signal or the activity signalcomprise at least one of a derived signal, a time averaged signal, afiltered signal or a raw signal.

In many embodiments, the processor determines baseline values of thepatient for the at least two of the electrocardiogram signal, thehydration signal, the respiration signal or the activity signal. The atleast two of the electrocardiogram signal, the hydration signal, therespiration signal or the activity signal signals may comprise changesfrom the baseline values.

In many embodiments, the at least two of the electrocardiogram signal,the hydration signal, the respiration signal or the activity signalcomprise differences from baseline values of a patient population. Theimpending decompensation is detected in response to the differences fromthe baseline value of the patient population.

In many embodiments, the hydration signal comprises an impedance signaland the activity signal comprise an accelerometer signal.

In many embodiments, the activity signal may comprise an accelerometersignal to determine a posture of the patient. In specific embodiments,the accelerometer signal may comprise a three dimensional inclinationsignal to determine a three dimensional orientation of the patient.

In many embodiments, the processor system combines a temperature signalwith the at least two of the electrocardiogram signal, the hydrationsignal, the respiration signal or the activity signal to detect theimpending cardiac decompensation.

In many embodiments, the processor transmits the at least two of theelectrocardiogram signal, the hydration signal, the respiration signalor the activity signal to a remote site where the at least two of theelectrocardiogram signal, the hydration signal, the respiration signalor the activity signal are combined to detect the impending cardiacdecompensation.

In many embodiments, instructions are transmitted from a remote site toa processor supported with the patient. The processor combines at leasttwo of the electrocardiogram signal, the hydration signal, therespiration signal or the activity signal in response to theinstructions to detect the impending cardiac decompensation

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A shows a patient and a monitoring system comprising an adherentdevice, according to embodiments of the present invention;

FIG. 1B shows a bottom view of the adherent device as in FIG. 1Acomprising an adherent patch;

FIG. 1C shows a top view of the adherent patch, as in FIG. 1B;

FIG. 1D shows a printed circuit boards and electronic components overthe adherent patch, as in FIG. 1C;

FIG. 1D-1 shows an equivalent circuit that can be used to determineoptimal frequencies for determining patient hydration, according toembodiments of the present invention;

FIG. 1E shows batteries positioned over the printed circuit board andelectronic components as in FIG. 1D;

FIG. 1F shows a top view of an electronics housing and a breathablecover over the batteries, electronic components and printed circuitboard as in FIG. 1E;

FIG. 1G shows a side view of the adherent device as in FIGS. 1A to 1F;

FIG. 1H shown a bottom isometric view of the adherent device as in FIGS.1A to 1G;

FIG. 2A shows a method of predicting an impending cardiacdecompensation, according to embodiments of the present invention; and

FIGS. 3A and 3B show clinical data measured with an adherent patchdevice.

DETAILED DESCRIPTION OF THE INVENTION

Embodiments of the present invention provide systems and methods for thedetection of an impending cardiac decompensation. In many embodiments,the impending decompensation can be detected early enough to avoid, orat least delay, the impending decompensation, such that patient traumaand/or expensive ICU care can be avoided. Although embodiments makespecific reference to monitoring impedance and electrocardiogram signalswith an adherent patch, the system methods and device described hereinmay be applicable to many applications in which physiological monitoringis used, for example wireless physiological monitoring with implantedsensors for extended periods. In some embodiments, implanted sensors maybe used, for example as described in U.S. Pat. Nos. 6,208,894;6,315,721; 6,185,452; and U.S. Application No. 60/972,329, entitled“Injectable Device for Physiological Monitoring” filed on Sep. 14, 2007,the same day as the present application with the same assignee, the fulldisclosures of which are incorporated by reference.

Decompensation is failure of the heart to maintain adequate bloodcirculation. Although the heart can maintain at least some pumping ofblood, the quantity is inadequate to maintain healthy tissues. Severalsymptoms can result from decompensation including pulmonary congestion,breathlessness, faintness, cardiac palpitation, edema of theextremities, and enlargement of the liver. Cardiac decompensation canresult in slow or sudden death. Sudden Cardiac Arrest (hereinafter“SCA”), also referred to as sudden cardiac death, is an abrupt loss ofcardiac pumping function that can be caused by a ventricular arrhythmia,for example ventricular tachycardia and/or ventricular fibrillation.Although decompensation and SCA can be related in that patients withdecompensation are also at an increased risk for SCA, decompensation isprimarily a mechanical dysfunction caused by inadequate blood flow, andSCA is primarily an electrical dysfunction caused by inadequate and/orinappropriate electrical signals of the heart.

FIG. 1A shows a patient P and a monitoring system 10. Patient Pcomprises a midline M, a first side S1, for example a right side, and asecond side S2, for example a left side. Monitoring system 10 comprisesan adherent device 100. Adherent device 100 can be adhered to a patientP at many locations, for example thorax T of patient P. In manyembodiments, the adherent device may adhere to one side of the patient,from which data from the one side can be collected. Work in relationwith embodiments of the present invention suggests that location on aside of the patient can provide comfort for the patient while the deviceis adhered to the patient.

Monitoring system 10 includes components to transmit data to a remotecenter 106. Adherent device 100 can communicate wirelessly to anintermediate device 102, for example with a single wireless hop from theadherent device on the patient to the intermediate device. Intermediatedevice 102 can communicate with remote center 106 in many ways, forexample with an internet connection. In many embodiments, monitoringsystem 10 comprises a distributed processing system with at least oneprocessor on device 100, at least one processor on intermediate device102, and at least one process at remote center 106, each of whichprocessors is in electronic communication with the other processors.Remote center 106 can be in communication with a health care provider108A with a communication system 107A, such as the Internet, anintranet, phone lines, wireless and/or satellite phone. Health careprovider 108A, for example a family member, can be in communication withpatient P with a communication, for example with a two way communicationsystem, as indicated by arrow 109A, for example by cell phone, email,landline. Remote center 106 can be in communication with a health careprofessional, for example a physician 108B, with a communication system107B, such as the Internet, an intranet, phone lines, wireless and/orsatellite phone. Physician 108B can be in communication with patient Pwith a communication, for example with a two way communication system,as indicated by arrow 109B, for example by cell phone, email, landline.Remote center 106 can be in communication with an emergency responder108C, for example a 911 operator and/or paramedic, with a communicationsystem 107C, such as the Internet, an intranet, phone lines, wirelessand/or satellite phone. Emergency responder 108C can travel to thepatient as indicated by arrow 109C. Thus, in many embodiments,monitoring system 10 comprises a closed loop system in which patientcare can be monitored and implemented from the remote center in responseto signals from the adherent device.

In many embodiments, the adherent device may continuously monitorphysiological parameters, communicate wirelessly with a remote center,and provide alerts when necessary. The system may comprise an adherentpatch, which attaches to the patient's thorax and contains sensingelectrodes, battery, memory, logic, and wireless communicationcapabilities. In some embodiments, the patch can communicate with theremote center, via the intermediate device in the patient's home. In themany embodiments, the remote center receives the data and applies theprediction algorithm. When a flag is raised, the center may communicatewith the patient, hospital, nurse, and/or physician to allow fortherapeutic intervention to prevent decompensation.

The adherent device may be affixed and/or adhered to the body in manyways. For example, with at least one of the following an adhesive tape,a constant-force spring, suspenders around shoulders, a screw-inmicroneedle electrode, a pre-shaped electronics module to shape fabricto a thorax, a pinch onto roll of skin, or transcutaneous anchoring.Patch and/or device replacement may occur with a keyed patch (e.g.two-part patch), an outline or anatomical mark, a low-adhesive guide(place guide remove old patch place new patch remove guide), or a keyedattachment for chatter reduction. The patch and/or device may comprisean adhesiveless embodiment (e.g. chest strap), and/or a low-irritationadhesive model for sensitive skin. The adherent patch and/or device cancomprise many shapes, for example at least one of a dogbone, anhourglass, an oblong, a circular or an oval shape.

In many embodiments, the adherent device may comprise a reusableelectronics module with replaceable patches (the module collectscumulative data for approximately 90 days) and/or the entire adherentcomponent (electronics+patch) may be disposable. In a completelydisposable embodiment, a “baton” mechanism may be used for data transferand retention, for example baton transfer may include baselineinformation. In some embodiments, the device may have a rechargeablemodule, and may use dual battery and/or electronics modules, wherein onemodule 101A can be recharged using a charging station 103 while theother module 101B is placed on the adherent device. In some embodiments,the intermediate device 102 may comprise the charging module, datatransfer, storage and/or transmission, such that one of the electronicsmodules can be placed in the intermediate device for charging and/ordata transfer while the other electronics module is worn by the patient.

In many embodiments, the system can perform the following functions:initiation, programming, measuring, storing, analyzing, communicating,predicting, and displaying. The adherent device may contain a subset ofthe following physiological sensors: bioimpedance, respiration,respiration rate variability, heart rate (average, minimum, maximum),heart rhythm, HRV, HRT, heart sounds (e.g. S3), respiratory sounds,blood pressure, activity, posture, wake/sleep, orthopnea,temperature/heat flux, and weight. The activity sensor may be one of thefollowing: ball switch, accelerometer, minute ventilation, HR,bioimpedance noise, skin temperature/heat flux, BP, muscle noise,posture.

In many embodiments, the patch wirelessly communicates with a remotecenter. In some embodiments, the communication may occur directly (via acellular or Wi-Fi network), or indirectly through intermediate device102. Intermediate device 102 may consist of multiple devices whichcommunicate wired or wirelessly to relay data to remote center 106.

FIG. 1B shows a bottom view of adherent device 100 as in FIG. 1Acomprising an adherent patch 110. Adherent patch 110 comprises a firstside, or a lower side 11 OA, that is oriented toward the skin of thepatient when placed on the patient. In many embodiments, adherent patch110 comprises a tape 110T which is a material, preferably breathable,with an adhesive 116A. Patient side 11 OA comprises adhesive 116A toadhere the patch 110 and adherent device 100 to patient P. Electrodes112A, 112B, 112C and 112D are affixed to adherent patch 110. In manyembodiments, at least four electrodes are attached to the patch, forexample six electrodes. In some embodiments the patch comprises at leasttwo electrodes, for example two electrodes to measure anelectrocardiogram (ECG) of the patient. Gel 114A, gel 114B, gel 114C andgel 114D can each be positioned over electrodes 112A, 112B, 112C and112D, respectively, to provide electrical conductivity between theelectrodes and the skin of the patient. In many embodiments, theelectrodes can be affixed to the patch 110, for example with knownmethods and structures such as rivets, adhesive, stitches, etc. In manyembodiments, patch 110 comprises a breathable material to permit airand/or vapor to flow to and from the surface of the skin.

FIG. 1C shows a top view of the adherent patch 100, as in FIG. 1B.Adherent patch 100 comprises a second side, or upper side 110B. In manyembodiments, electrodes 110A, 110B, 110C and 110D extend from lower side110A through the adherent patch to upper side 110B. In some embodiments,an adhesive 116B can be applied to upper side 110B to adhere structures,for example, a cover, to the patch such that the patch can support theelectronics and other structures when the patch is adhered to thepatient. The printed circuit board (PCB) comprise completely flex PCB,rigid PCB combined flex PCB and/or rigid PCB boards connected by cable.

FIG. 1D shows a printed circuit boards and electronic components overadherent patch 110, as in FIG. 1C. A printed circuit board (PCB), forexample flex PCB 120, can be positioned above 110B of patch 110. FlexPCB 120 can include traces that extends to connectors 122A, 122B, 122Cand 122D on the flex PCB. Connectors 122A, 122B, 122C and 122D can bepositioned on flex PCB 120 in alignment with electrodes 112A, 112B, 112Cand 112D so as to electrically couple the flex PCB with the electrodes.In some embodiments, connectors 122A, 122B, 122C and 122D may compriseinsulated wires or a flex circuit that provide strain relief between thePCB and the electrodes. In some embodiments, additional PCB's forexample PCB 120A, 120B, 120C and 120D be connected to flex PCB 120.Electronic components 130 can be connected to flex PCB 120 and/ormounted thereon. In some embodiments, electronic components 130 can bemounted on the additional PCB's.

Electronic components 130 comprise components to take physiologicmeasurements, transmit data to remote center 106 and receive commandsfrom remote center 106. In many embodiments, electronics components 130may comprise known low power circuitry, for example complementary metaloxide semiconductor (CMOS) circuitry components. Electronics components130 comprise an activity sensor and activity circuitry 134, impedancecircuitry 136 and electrocardiogram circuitry, for example ECG circuitry136. In some embodiments, electronics circuitry 130 may comprise amicrophone and microphone circuitry 142 to detect an audio signal fromwithin the patient, and the audio signal may comprise a heart soundand/or a respiratory sound, for example an S3 heart sound and arespiratory sound with rales and/or crackles. Electronics circuitry 130may comprise a temperature sensor, for example a thermistor, andtemperature sensor circuitry 144 to measure a temperature of thepatient, for example a temperature of a skin of the patient. Electronicscircuitry may comprise a heat flux sensor and heat flux sensor circuitryto measure a skin heat flow of a patient.

Work in relation to embodiments of the present invention suggests thatskin temperature may effect impedance and/or hydration measurements, andthat skin temperature measurements may be used to correct impedanceand/or hydration measurements. In some embodiments, increase in skintemperature can be associated with increased vaso-dilation near the skinsurface, such that measured impedance measurement decreased, eventhrough the hydration of the patient in deeper tissues under the skinremains substantially unchanged. Thus, use of the temperature sensor canallow for correction of the hydration signals to more accurately assessthe hydration, for example extra cellular hydration, of deeper tissuesof the patient, for example deeper tissues in the thorax.

Electronics circuitry 130 may comprise a processor 146. Processor 146comprises a tangible medium, for example read only memory (ROM),electrically erasable programmable read only memory (EEPROM) and/orrandom access memory (RAM). Electronic circuitry 130 may comprise realtime clock and frequency generator circuitry 148. In some embodiments,processor 136 may comprise the frequency generator and real time clock.The processor can be configured to control a collection and transmissionof data from the impedance circuitry electrocardiogram circuitry and theaccelerometer. In many embodiments, device 100 comprise a distributedprocessor system, for example with multiple processors on device 100.

In many embodiments, electronics components 130 comprise wirelesscommunications circuitry 132 to communicate with remote center 106. Thewireless communication circuitry can be coupled to the impedancecircuitry, the electrocardiogram circuitry and the accelerometer totransmit to a remote center with a communication protocol at least oneof the hydration signal, the electrocardiogram signal or theaccelerometer signal. In specific embodiments, wireless communicationcircuitry is configured to transmit the hydration signal, theelectrocardiogram signal and the accelerometer signal to the remotecenter with a single wireless hop, for example from wirelesscommunication circuitry 132 to intermediate device 102. Thecommunication protocol comprises at least one of Bluetooth, Zigbee,WiFi, WiMax, IR, amplitude modulation or frequency modulation. In manyembodiments, the communications protocol comprises a two way protocolsuch that the remote center is capable of issuing commands to controldata collection.

In some embodiments, intermediate device 102 comprises a data collectionsystem to collect and store data from the wireless transmitter. The datacollection system can be configured to communicate periodically with theremote center. In many embodiments, the data collection system cantransmit data in response to commands from remote center 106 and/or inresponse to commands from the adherent device.

Activity sensor and activity circuitry 134 can comprise many knownactivity sensors and circuitry. In many embodiments, the accelerometercomprises at least one of a piezoelectric accelerometer, capacitiveaccelerometer or electromechanical accelerometer. The accelerometer maycomprise a 3-axis accelerometer to measure at least one of aninclination, a position, an orientation or acceleration of the patientin three dimensions. Work in relation to embodiments of the presentinvention suggests that three dimensional orientation of the patient andassociated positions, for example sitting, standing, lying down, can bevery useful when combined with data from other sensors, for example ECGdata and/or hydration data.

Impedance circuitry 136 can generate both hydration data and respirationdata. In many embodiments, impedance circuitry 136 is electricallyconnected to electrodes 112A, 112B, 112C and 112D such that electrodes112A and 112D comprise outer electrodes that are driven with a current,or force electrodes. The current delivered between electrodes 112A and112D generates a measurable voltage between electrodes 112B and 112C,such that electrodes 112B and 112C comprise inner electrodes, or senseelectrodes that measure the voltage in response to the current from theforce electrodes. The voltage measured by the sense electrodes can beused to determine the hydration of the patient.

FIG. 1D-1 shows an equivalent circuit 152 that can be used to determineoptimal frequencies for measuring patient hydration. Work in relation toembodiments of the present invention indicates that the frequency of thecurrent and/or voltage at the force electrodes can be selected so as toprovide impedance signals related to the extracellular and/orintracellular hydration of the patient tissue. Equivalent circuit 152comprises an intracellular resistance 156, or R(ICW) in series with acapacitor 154, and an extracellular resistance 158, or R(ECW).Extracellular resistance 158 is in parallel with intracellularresistance 156 and capacitor 154 related to capacitance of cellmembranes. In many embodiments, impedances can be measured and provideuseful information over a wide range of frequencies, for example fromabout 0.5 kHz to about 200 KHz. Work in relation to embodiments of thepresent invention suggests that extracellular resistance 158 can besignificantly related extracellular fluid and to cardiac decompensation,and that extracellular resistance 158 and extracellular fluid can beeffectively measured with frequencies in a range from about 0.5 kHz toabout 20 kHz, for example from about 1 kHz to about 10 kHz. In someembodiments, a single frequency can be used to determine theextracellular resistance and/or fluid. As sample frequencies increasefrom about 10 kHz to about 20 kHz, capacitance related to cell membranesdecrease the impedance, such that the intracellular fluid contributes tothe impedance and/or hydration measurements. Thus, many embodiments ofthe present invention employ measure hydration with frequencies fromabout 0.5 kHz to about 20 kHz to determine patient hydration.

In many embodiments, impedance circuitry 136 can be configured todetermine respiration of the patient. In specific embodiments, theimpedance circuitry can measure the hydration at 25 Hz intervals, forexample at 25 Hz intervals using impedance measurements with a frequencyfrom about 0.5 kHz to about 20 kHz.

ECG circuitry 138 can generate electrocardiogram signals and data fromelectrodes 112A, 112B, 112C and 112D. In some embodiments, ECG circuitry138 is connected to inner electrodes 12B and 122C, which may comprisesense electrodes of the impedance circuitry as described above. In someembodiments, the inner electrodes may be positioned near the outerelectrodes to increase the voltage of the ECG signal measured by ECGcircuitry 138. In some embodiments, the ECG circuitry can sharecomponents with the impedance circuitry.

FIG. 1E shows batteries 150 positioned over the flex printed circuitboard and electronic components as in FIG. 1D. Batteries 150 maycomprise rechargeable batteries that can be removed and/or recharged. Insome embodiments, batteries 150 can be removed from the adherent patchand recharged and/or replaced.

FIG. 1F shows a top view of a cover 162 over the batteries, electroniccomponents and flex printed circuit board as in FIG. 1E. In manyembodiments, an electronics housing 160 may be disposed under cover 162to protect the electronic components, and in some embodimentselectronics housing 160 may comprise an encapsulant over the electroniccomponents and PCB. In many embodiments, electronics housing 160 maycomprise a water proof material, for example a sealant adhesive such asepoxy or silicone coated over the electronics components and/or PCB. Insome embodiments, electronics housing 160 may comprise metal and/orplastic, which may be potted with silicone, epoxy, etc.

Cover 162 may comprise many known biocompatible cover, casing and/orhousing materials, such as elastomers, for example silicone. Theelastomer may be fenestrated to improve breathability. In someembodiments, cover 162 may comprise many known breathable materials, forexample polyester or polyamide fabric. The breathable fabric may becoated to make it water resistant, waterproof, and/or to aid in wickingmoisture away from the patch. The breathable fabric may be coated inorder to make the outside hydrophobic and the inside hydrophilic.

FIG. 1G shows a side view of adherent device 100 as in FIGS. 1A to 1F.Adherent device 100 comprises a maximum dimension, for example a length170 from about 4 to 10 inches (from about 100 mm to about 250 mm), forexample from about 6 to 8 inches (from about 150 mm to about 200 mm). Insome embodiments, length 170 may be no more than about 6 inches (no morethan about 150 mm). Adherent device 100 comprises a thickness 172.Thickness 172 may comprise a maximum thickness along a profile of thedevice. Thickness 172 can be from about 0.2 inches to about 0.4 inches(from about 5 mm to about 10 mm), for example about 0.3 inches (about7.5 mm).

FIG. 1H shown a bottom isometric view of adherent device 100 as in FIGS.1A to 1G. Adherent device 100 comprises a width 174, for example amaximum width along a width profile of adherent device 100. Width 174can be from about 2 to about 4 inches (from about 50 mm to 100 mm), forexample about 3 inches (about 75 mm).

FIG. 2A shows a method 200 of predicting an impending cardiacdecompensation. A step 205 measures an ECG signal. The ECG signal maycomprise a differential signal measured with at least two electrodes andmay be measured in many known ways. A step 210 measures an hydrationsignal. The hydration signal may comprise an impedance signal, forexample a four pole impedance signal, and may be measured in many knownways. A step 215 measures a respiration signal. The respiration signalmay comprise an impedance signal, and may be measured in many knownways. A step 220 measures an activity signal. The activity signal may bemeasured in many known ways and may comprise a three dimensionalaccelerometer signal to determine a position of the patient, for examplefrom a three dimensional accelerometer signal. A step 225 measures atemperature signal. The temperature signal may be measured in many ways,for example with a thermistor, a thermocouple, and known temperaturemeasurement devices. A step 230 records a time of day of the signals,for example a local time of day such as morning, afternoon, evening,and/or nighttime.

A step 235 processes the signals. The signals may be processed in manyknown ways, for example to generate at least one of a derived signal, atime averaged signal, a filtered signal. In some embodiments, thesignals may comprise raw signals. The ECG signal may comprise at leastone of a heart rate signal, a heart rate variability signal, an averageheart rate signal, a maximum heart rate signal or a minimum heart ratesignal. The hydration signal may comprise an impedance measurementsignal. The activity signal may comprise at least one of anaccelerometer signal, a position signal indicating the orientation ofthe patient, such as standing, lying, or sitting. The respiration signalmay comprise a least one of a respiration rate, a maximum respirationrate, a minimum respiration rate, an average respiration rate orrespiration rate variability. The temperature may comprise an averagetemperature or a peak temperature.

A step 240 compares the signals with baseline values. In manyembodiments, the baseline values may comprise measurements from the samepatient at an earlier time. In some embodiments, the baseline valuescomprise values for a patient population. In some embodiments, thebaseline values for a patient population may comprise empirical datafrom a suitable patient population size, for example at least about 144patients, depending on the number of variables measured, statisticalconfidence and power used. The measured signals may comprise changesand/or deviations from the baseline values.

A step 245 transmits the signals. In many embodiments, the measurementsignals, which may comprise derived and/or processed measurementsignals, are transmitted to the remote site for comparison. In someembodiments, the signals may be transmitted to a processor supportedwith the patient for comparison.

A step 250 combines at least two of the ECG signal, the hydrationsignal, the respiration signal, the activity signal and the temperaturesignal to detect the impending decompensation. In many embodiments, atleast three of the signals are combined. In some embodiments, at leastfour signals comprising ECG signal, the hydration signal, therespiration signal and the activity signal are combined to detect theimpending decompensation. In specific embodiments, at least four signalscomprising the ECG signal, the hydration signal, the respiration signal,the activity signal and the temperature signal are combined to detectthe impending decompensation.

The signals can be combined in many ways. In some embodiments, thesignals can be used simultaneously to determine the impending cardiacdecompensation.

In some embodiments, the signals can be combined by using the at leasttwo of the electrocardiogram signal, the hydration signal, therespiration signal or the activity signal to look up a value in apreviously existing array.

TABLE 1 Lookup Table for ECG and Hydration Signals Heart Rate Hydration0-49 bpm 50-69 bpm 70-90 bpm   >60 Ohms N N Y 41-59 Ohms N Y Y  0-40Ohms Y Y Y

Table 1 shows combination of the electrocardiogram signal with thehydration signal to look up a value in a pre-existing array. For exampleat a heart rate of 89 bpm and a hydration of 35 Ohms, the value in thetable may comprise Y. In specific embodiments, the values of the look uptable can be determined in response to empirical data measured for apatient population of at least about 100 patients, for examplemeasurements on about 1000 to 10,000 patients.

In some embodiments, the table may comprise a three or more dimensionallook up table.

In some embodiments, the signals may be combined with at least one ofadding, subtracting, multiplying, scaling or dividing the at least twoof the electrocardiogram signal, the hydration signal, the respirationsignal or the activity signal. In specific embodiments, the measurementsignals can be combined with positive and or negative coefficientsdetermined in response to empirical data measured for a patientpopulation of at least about 100 patients, for example data on about1000 to 10,000 patients.

In some embodiments, a weighted combination may combine at least 3measurement signals to generate an output value according to a formulaof the general form

OUTPUT=aX+bY+cZ

where a, b and c comprise positive or negative coefficients determinedfrom empirical data and X, Y and Z comprise measured signals for thepatient, for example at least three of the electrocardiogram signal, thehydration signal, the respiration signal or the activity signal. Whilethree coefficients and three variables are shown, the data may becombined with multiplication and/or division. One or more of thevariables may be the inverse of a measured variable.

In some embodiments, the ECG signal comprises a heart rate signal thatcan be divided by the activity signal. Work in relation to embodimentsof the present invention suggest that an increase in heart rate with adecrease in activity can indicate an impending decompensation. Thesignals can be combined to generate an output value with an equation ofthe general form

OUTPUT=aX/Y+bZ

where X comprise a heart rate signal, Y comprises a hydration ratesignal and Z comprises a respiration signal, with each of thecoefficients determined in response to empirical data as describedabove.

In some embodiments, the data may be combined with a tiered combination.While many tiered combinations can be used a tiered combination withthree measurement signals can be expressed as

OUTPUT=(ΔX)+(ΔY)+(ΔZ)

where (ΔX), (ΔY), (ΔZ) may comprise change in heart rate signal frombaseline, change in hydration signal from baseline and change inrespiration signal from baseline, and each may have a value of zero orone, based on the values of the signals. For example if the heart rateincrease by 10%, (ΔX) can be assigned a value of 1. If hydrationincreases by 5%, (ΔY) can be assigned a value of 1. If activitydecreases below 10% of a baseline value (ΔZ) can be assigned a valueof 1. When the output signal is three, a flag may be set to trigger analarm.

In some embodiments, the data may be combined with a logic gatedcombination. While many logic gated combinations can be used a logicgated combination with three measurement signals can be expressed as

OUTPUT=(ΔX)AND(ΔY)AND(ΔZ)

where (ΔX), (ΔY), (ΔZ) may comprise change in heart rate signal frombaseline, change in hydration signal from baseline and change inrespiration signal from baseline, and each may have a value of zero orone, based on the values of the signals. For example if the heart rateincrease by 10%, (ΔX) can be assigned a value of 1. If hydrationincreases by 5%, (ΔY) can be assigned a value of 1. If activitydecreases below 10% of a baseline value (ΔZ) can be assigned a valueof 1. When each of (ΔX), (ΔY), (ΔZ) is one, the output signal is one,and a flag may be set to trigger an alarm. If any one of (ΔX), (ΔY) or(ΔZ) is zero, the output signal is zero and a flag may be set so as notto trigger an alarm. While a specific example with AND gates has beenshown the data can be combined in may ways with known gates for exampleNAND, NOR, OR, NOT, XOR, XNOR gates. In some embodiments, the gatedlogic may be embodied in a truth table.

A step 255 sets a flag. The flag can be set in response to the output ofthe combined signals. In some embodiments, the flag may comprise abinary parameter in which a value of zero does not triggers an alarm anda value of one triggers an alarm.

A step 260 communicates with the patient and/or a health care provider.In some embodiments, the remote site may contact the patient todetermine if he or she is okay and communicate the impendingdecompensation such that the patient can receive needed medical care. Insome embodiments, the remote site contacts the health care provider towarn the provider of the impending decompensation and the need for thepatient to receive medical care.

A step 265 collects additional measurements. Additional measurements maycomprise additional measurements with the at least two signals, forexample with greater sampling rates and or frequency of themeasurements. Additional measurements may comprise measurements with aadditional sensors, for example an onboard microphone to detect at leastone of rales, S1 heart sounds, S2 heart sounds, S3 heart sounds, orarrhythmias. In some embodiments, the additional measurements, forexample sounds, can be transmitted to the health care provider todiagnose the patient in real time.

The processor system, as described above, can be configured to performthe method 200, including many of the steps described above. It shouldbe appreciated that the specific steps illustrated in FIG. 2A provide aparticular method of predicting an impending cardiac decompensation,according to an embodiment of the present invention. Other sequences ofsteps may also be performed according to alternative embodiments. Forexample, alternative embodiments of the present invention may performthe steps outlined above in a different order. Moreover, the individualsteps illustrated in FIG. 2A may include multiple sub-steps that may beperformed in various sequences as appropriate to the individual step.Furthermore, additional steps may be added or removed depending on theparticular applications. One of ordinary skill in the art wouldrecognize many variations, modifications, and alternatives.

Experimental Clinical Study

The protocol below has been used to measure signals from actual patientswith an adherent device. These data show that an adherent patch asdescribed above can be continuously adhered for at least one week. Thesedata also show that 90 day continuous in home monitoring can be achievedwith a set of 13 patches in which one of the patches is replaced eachweek. The clinical testing device used an adherent device withmodifications, as described more fully below and referred to as the MSsystem (multi-sensor). Although the clinical device did not includewireless circuitry and processor circuitry supported with the patchadhered to the skin of the patient, these data do show that such adevice, as described above, can be made by one of ordinary skill in theart based on the teachings described herein. Additional empiricalstudies can be conducted on a suitable number of patients.

MS Clinical System Description

The MS clinical system includes many of the structure componentsdescribed above. There is a flexible connection between the electrodesand the flex PCB, for example wires or polyurethane with silver ink. Thecover can stretch with the breathable tape on both the clinical deviceand the above described wireless device. There is generally a gapbetween the flex PCB and breathable tape in both clinical and abovedescribed wireless devices. The tested device used weights to at leastpartially simulate the weight of wireless and processor circuitry. Theadherent device of the MS clinical system comprises four electrodes tomeasure bioimpedance and ECG signals and a 3-axis accelerometer, asdescribed above. Bioimpedance signals were used to determine patientrespiration and patient hydration, and accelerometer signals were usedto determine patient activity and posture. The MS clinical adherentpatch device comprising the sensors and at least some sensor circuitrywere connected to a processor to record data. The processor wasconnected to the tested adherent device with wires and supported awayfrom the tested adherent patch device, for example around the patient'swaist. Data were collected at regular intervals and uploaded to a remotesite, as described above.

Clinical testing of the MS clinical system shows the effectiveness ofthe structures for continuous adherence of at least one week and datacollection, and that patches can be successively removed and replaced bythe patient for in-home monitoring. This effectiveness has been shownwithout requiring fully functional electronics circuitry such as abattery, wireless circuitry and process circuitry on the adherentdevice. For example, the MS system includes an insert with about 20 g ofadditional weight. Although an insert with a 20 gram weight was used forthe MS clinical device, greater amounts of weight and circuitry can beused, for example about 30-50 g. The patch device may be modified toaccommodate additional weight, for example by increasing the size of theadherent surface. The shape of the MS clinical patch is generallyelongate, similar to the elongate shape shown above.

Study Design and Rationale

The MS System is used in a clinical study of heart failure patients togather data that can be used to develop an algorithm for diagnosing andpredicting impending heart failure decompensation events. Eventstypically manifest as heart failure-related hospitalization, emergencyroom or urgent care visits leading to a change in oral or IV diuretictreatment.

The purpose of the clinical study is to correlate physiological signalsrecorded by the system to clinical events of acute heart failuredecompensation (AHFD). Signals from the patch can be weighted andcombined to determine an’ index that associates physiologic parametersto impending events of decompensation. Patients who have been classifiedas New York Heart Association class III and IV within the last 12 monthsand have had a recent AHFD event can be enrolled into the study and aremonitored with the MS system for approximately 90 days.

AHFD events are defined as any of the following:

1) Any heart failure related ER, Urgent Care, in-office visit orhospitalization requiring administration of IV diuretics, administrationof IV inotropes, or ultrafiltration for fluid removal.

2) A change in diuretic, defined as a change in diuretic directed by thehealth care provider occurring inside a hospital, emergency room, orurgent care setting (i.e. no patient self-directed changes tomedications not approved by a health care provider would be included),that satisfies one or more of the following: a) a change in the type ofdiuretic the patient is taking, b) a dose increase of an existingdiuretic, or c) the addition of another diuretic.

3) A heart failure decompensation event for which death is the outcome.

Patients enrolled in the study were asked to replace the patch weekly.The study can enroll at least about 550 patients. The patient wasprovided with a kit comprising 13 patches for replacement. The patcheswere placed on alternating left and right sides of the patient's thorax,as described above, to minimize progressive irritation.

The data collected in the study can be used to develop an algorithm toat least one of detect, diagnose or predict an impending cardiacdecompensation. The algorithm can be implemented on a processor systemas described above. Known methods can be used to analyze the data, forexample splitting the patients into two groups, one to developparameters for the algorithm and a second group to test the algorithmdeveloped with the first group. In many embodiments, the signal of thealgorithm may comprise a simple binary output for impending cardiacdecompensation of the patient. The logic output, yes or no, can bedetermined in response to patient data combined as described above. Thelogic output may comprise a signal, such as a binary Y or N signal.

The developed algorithm can be evaluated with composite sensitivity andfalse positive patient signal status rates. The sensitivity may bedefined as the percent of true positive events out of all conditionpresent events, and the false positive patient status signal status ratecan be defined as the number of false positive patient status signalsper patient-years of follow up. For example, the sensitivity can be atleast 50%, for example at least 60%, at least 70%, or even at least 80%.The false positive patient signal status rate may be limited to no morethan about 1.1 false positive patient status signals per patient year,for example no more than about 1.0 false positive patient status signalsper patient year, no more than about 0.9 false positive patient statussignals per patient year, and even no more than about 0.8 false positivepatient status signals per patient year.

Clinical Results

Clinical data are available for the first 180 patients enrolled in thestudy.

FIGS. 3A and 3B show clinical data measured with an adherent patchdevice, in accordance with the above protocol. FIG. 3A shows data from apatient with the MS patch adhered to a first patient, and the data wasacquired over the 90 day period with the series of 13 patches. Thesignals measured included Heart Rate (beats per minute), Heart RateVariability (ms), Respiratory Rate (breaths per minute), Activity(m-G's) and Body Fluid (Ohms). FIG. 3B shows data from a second patientsimilar to FIG. 3A.

Of the 180 patients who have completed the study with the MS adherentpatch, as described above, all patches in all patients adheredcontinuously without patch failure. In all patients, the first patchadhered continuously for the first week. With the exception of a handfulof patient deaths and early withdrawals that were unrelated to devicefailure, all patients reached the end of 90-day follow-up period havingused 13 weekly patches without incident. None of the 180 patients showedskin irritation or damage that required withdrawal from the study.

The above data show that the wireless adherent patch device can beconstructed for in home wireless patient monitoring for an extendedperiod of at least 90 day, in which each patch of a set is continuouslyadhered to a patient for at least one week and each patch is configuredto support the measurement circuitry, the processor, the wirelesscommunication circuitry and the battery with the skin of the patient.

While the exemplary embodiments have been described in some detail, byway of example and for clarity of understanding, those of skill in theart will recognize that a variety of modifications, adaptations, andchanges may be employed. Hence, the scope of the present inventionshould be limited solely by the appended claims.

1. A system to detect impending acute cardiac decompensation of apatient, the system comprising: impedance circuitry to measure ahydration signal of the patient, wherein the hydration signalcorresponds to a tissue hydration of the patient; activity sensor tomeasure an activity level of the patient; and a processor systemcomprising a computer readable memory in communication with theimpedance circuitry and the activity sensor, wherein the computerreadable memory of the processor system embodies instructions to combinethe hydration signal and the activity level of the patient to detect theimpending acute cardiac decompensation.
 2. The system of claim 1,wherein the activity signal comprises an accelerometer signal todetermine at least one of inclination, position, orientation, andacceleration of the patient.
 3. The system of claim 1, furtherincluding: additional sensing circuitry to measure additionalphysiological parameters in response to a detected impending acutecardiac decompensation.
 4. The system of claim 3, wherein the additionalsensing circuitry includes an onboard microphone to detect at least oneof rales, heart sounds, and/or arrhythmias.
 5. The system of claim 1,further including: electrocardiogram circuitry coupled to at least twoof the four electrodes and configured to measure an electrocardiogramsignal of the patient, wherein the processor system utilizes theelectrocardiogram signal in combination with the calculated hydrationmeasurement and activity level of the patient to predict an impendingacute cardiac decompensation of the patient.
 6. The system of claim 1,wherein the impedance circuitry is utilized to measure a respirationsignal of the patient, wherein the processor system further utilizes themeasured respiration signal in combination with the measured hydrationsignal and the activity level of the patient to detect the impendingacute cardiac decompensation.
 7. A method of detecting decompensation ina patient, the method comprising: measuring a hydration signal of thepatient with impedance circuitry and a plurality of electrodes affixedto the patient, wherein the hydration signal corresponds to a tissuehydration of the patient; measuring an activity level of the patientwith an activity sensor; and combining the hydration signal and theactivity level of the patient to detect the impending acute cardiacdecompensation.
 8. The method of claim 7, wherein the activity signalcomprises an accelerometer signal that is used to determine at least oneof inclination, position, orientation, and acceleration of the patient.9. The method of claim 7, wherein in response to a detected impendingacute cardiac decompensation, the method further includes measuringadditional physiological parameters.
 10. The method of claim 9, whereinthe additional physiological parameters includes one or more of rales,heart sounds, and/or arrhythmias.
 11. The method of claim 7, furtherincluding: measuring electrocardiogram signals of the patient withelectrocardiogram circuitry coupled to at least two of the plurality ofelectrodes, wherein the electrocardiogram signals are combined with themeasured hydration signal and activity signal to predict an impendingacute cardiac decompensation of the patient.
 12. The method of claim 7,further including: measuring a respiration signal of the patient withthe impedance circuitry, wherein the respiration signal is combined withthe measured hydration signal and activity signal to predict animpending acute cardiac decompensation of the patient.
 13. A system todetect impending acute cardiac decompensation of a patient, the systemcomprising: impedance circuitry to measure a respiration signal of thepatient; activity sensor to measure an activity level of the patient,wherein the activity signal comprises an accelerometer signal todetermine at least one of inclination, position, orientation, andacceleration of the patient; and a processor system comprising acomputer readable memory in communication with the impedance circuitryand the activity sensor, wherein the computer readable memory of theprocessor system embodies instructions to combine the respiration signaland the activity level of the patient to detect the impending acutecardiac decompensation.
 14. The system of claim 13, further including:additional sensing circuitry to measure additional physiologicalparameters in response to a detected impending acute cardiacdecompensation.
 15. The system of claim 14, wherein the additionalsensing circuitry includes an onboard microphone to detect at least oneof rales, heart sounds, and/or arrhythmias.
 16. The system of claim 14,further including: electrocardiogram circuitry coupled to at least twoof the four electrodes and configured to measure an electrocardiogramsignal of the patient, wherein the processor system utilizes theelectrocardiogram signal in combination with the calculated hydrationmeasurement and posture information to predict an impending acutecardiac decompensation of the patient.
 17. The system of claim 13,wherein the impedance circuitry is utilized to measure a hydrationsignal of the patient, wherein the processor system further utilizes themeasured hydration signal in combination with the measured respirationsignal and the activity level of the patient to detect the impendingacute cardiac decompensation.